Familial intrahepatic cholestasis (FIC) encompasses a genetically heterogeneous group of autosomal recessive liver disorders characterized by impaired bile formation and secretion, leading to progressive cholestasis, liver injury, and eventual hepatic failure. The most well-defined subset, progressive familial intrahepatic cholestasis (PFIC), includes multiple subtypes (PFIC1–PFIC6), each associated with mutations in distinct genes such as ATP8B1, ABCB11, ABCB4, TJP2, NR1H4, and MYO5B. These mutations disrupt hepatocellular transport mechanisms, particularly bile salt export and phospholipid translocation, resulting in toxic bile accumulation and hepatocellular damage. Clinically, PFIC presents in infancy or early childhood with jaundice, pruritus, growth failure, and hepatosplenomegaly, often progressing to cirrhosis and portal hypertension. Biochemical profiles vary by subtype, with PFIC1 and PFIC2 typically showing low gamma-glutamyl transferase (GGT), while PFIC3 exhibits elevated GGT due to biliary epithelial injury. Diagnosis relies on a combination of clinical features, liver histology, bile acid profiling, and genetic testing, which has become the gold standard for subtype classification. Management strategies include symptomatic relief of pruritus, nutritional support, and biliary diversion procedures. In advanced cases, liver transplantation remains the definitive treatment. Emerging therapies such as ileal bile acid transporter (IBAT) inhibitors and gene-targeted approaches offer promising avenues for disease modification.